To evaluate the efficacy and safety of eptinezumab for episodic migraine (EM) prevention through 1 year.

Eligible adults (EM, ICHD-II) were randomized to eptinezumab 30mg, 100mg, 300mg, or placebo, administered intravenously every 12 weeks for 4 infusions. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) over Weeks 1-12. Key secondary endpoints included: ≥75% migraine responder rates (RRs) over Week 1-4; ≥75% and ≥50% migraine RRs over Weeks 1-12.

Baseline mean MMDs were ~8.5 across groups in the efficacy population (N=888). In 100mg-treated patients, changes from baseline in MMDs were -3.9 (Months1-3; p=0.018), -4.5 (Months4-6), -4.7 (Months7-9), and -4.5 (Months10-12). The ≥75% migraine RRs were: 30.8% (p=0.011), 22.2% (NS), 33.5%, 40.3%, and 39.4% over Months1, 1-3, 4-6, 7-9, and 10-12, respectively. The ≥50% migraine RRs were: 49.8% (Months1-3; p=0.009), 62.0% (Months4-6), 63.8% (Months7-9), and 64.7% (Months10-12).

In 300mg-treated patients, changes from baseline in MMDs were -4.3 (Months1-3; p<0.001), -4.8 (Months4-6), -5.1 (Months7-9), and -5.3 (Months10-12). The ≥75% migraine RRs were: 31.5% (p=0.007), 29.7% (p<0.001), 40.1%, 43.2%, and 54.1% over Months1, 1-3, 4-6, 7-9, and 10-12, respectively. The ≥50% migraine RRs were: 56.3% (Months1-3; p<0.001), 65.3% (Months4-6), 69.8% (Months7-9), and 69.8% (Months10-12).

In placebo-treated patients, the change from baseline in MMDs was -3.2 (Months1-3), -3.8 (Months4-6), -4.0 (Months7-9), and -4.1 (Months10-12). The ≥75% migraine RRs were: 20.3% (Month1), 16.2% (Months1-3), 16.2% (Months4-6), 29.7% (Months7-9), and 39.6% (Months10-12). The ≥50% migraine RRs were: 37.4% (Months1-3), 51.4% (Months4-6), 58.1% (Months7-9), and 55.4% (Months10-12).

Treatment-emergent adverse event rates were similar between groups.

Eptinezumab reduced MMDs over the first 3 months with sustained or incremental reductions achieved with additional infusions. Migraine RRs were greater with eptinezumab vs placebo across dosing intervals.